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Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome
Head E, Lott IT, Hof PR, Bouras C, Su JH, Kim R, Haier R, Cotman CW.. Journal of neuropathology and experimental neurology, 2003-09-01
Topic: Brain proteins, microglia and lab models
Aged individuals with Down syndrome (DS) develop senile plaques and neurofibrillary tangles consistent with Alzheimer disease (AD). Prior to or in parallel with AD pathology, compensatory growth responses may occur. Immunohistochemistry and confocal microscopy studies in the hippocampus from 15 individuals ranging in age from 5 months to 67 years compared markers of normal and abnormal tau accumulation (phosphorylated tau [AT8, MC-1], tau-1, N-terminal tau) with the extent and location of neuronal growth marker immunoreactivity (BDNF, GAP-43, MAP-2). In middle age (30-40 years), prior to entorhinal neuron loss, the earliest tau accumulation occurred in the outer molecular layer (OML), which was consistent with both pathological and compensatory fetal tau expression. These events were followed at a later age, associated with entorhinal neuron loss, by an increase in GAP-43. Hilar neurons exhibiting a sprouting morphology were also noted. Age-dependent observations in the DS brain in the current study parallel hippocampal compensatory responses described in entorhinal cortex lesion studies in rodents. Thus, compensatory growth responses may occur in DS prior to extensive AD pathology and may be one mechanism underlying observations in PET studies of hypermetabolism in the entorhinal cortex of individuals with DS.
Key findings
- These events were followed at a later age, associated with entorhinal neuron loss, by an increase in GAP-43.
Why it matters
In hippocampal tissue from 15 people with Down syndrome aged 5 months to 67 years, the earliest tau accumulation in middle age occurred in the outer molecular layer, followed later by an increase in GAP-43 associated with entorhinal neuron loss. The authors suggest compensatory growth responses may occur before extensive Alzheimer's pathology, but this is an observational tissue study and does not test a treatment.
Study details
- Participants15
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2003 — older than 20 years, still counted |
| Sample size | 1 / 4 | 15 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 38 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 2 / 6 | Cited 1.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Carl W. Cotman: h-index 166 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Icahn School of Medicine at Mount Sinai: institution h-index 1,331 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 14533781) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Head, E., Lott, I. T., Hof, P. R., Bouras, C., Su, J. H., Kim, R., et al. (2003). Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome. Journal of neuropathology and experimental neurology. https://doi.org/10.1093/jnen/62.9.917
Vancouver
Head E, Lott IT, Hof PR, Bouras C, Su JH, Kim R, et al. Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome. Journal of neuropathology and experimental neurology. 2003. doi:10.1093/jnen/62.9.917. PMID: 14533781.
BibTeX
@article{head2003-14533781,
author = {Head, E. and Lott, I. T. and Hof, P. R. and Bouras, C. and Su, J. H. and Kim, R. and Haier, R. and Cotman, C. W.},
title = {{Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome}},
journal = {Journal of neuropathology and experimental neurology},
year = {2003},
doi = {10.1093/jnen/62.9.917},
pmid = {14533781},
url = {https://doi.org/10.1093/jnen/62.9.917}
}
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